Project 2. Antibody Cooperation for Fc-Fc-gamma Receptor (Fc?R)-mediated functions. Although intrinsic differences in Fc-FcR interactions exist between humans and RM, we hypothesize that similarities between the two species for engagement of the Fc?R-bearing cells can be defined to 1) select RM with Fc?R genotypes/phenotypes mediating antiviral functions that match those observed in humans; and 2) identify combinations of antibodies of multiple specificities, through highly selective Fc- Fc?R antibody interactions, that can act in concert to recruit Fc-gamma R-bearing cells similar to humans The overall Program hypothesis is that the RM model can be substantially improved for testing antibody-based interventions and vaccines through elucidation of key variables that impact species-specific FcgR-dependent effector functions (i.e. antibody epitope specificity, immune complex formation, isotype/subclass, glycosylation, and FcR genotype/phenotype. The specific aims for Project 2 are as follows: AIM 1. Define similarities and differences in Fc?R mediated Ab effector function between RM and humans. AIM 2. Determine the combination of antibodies that together can mediate superior antiviral function